Statins in the chemoprevention of colorectal cancer in established animal models of sporadic and colitis-associated cancer

Abstract

Despite the availability of effective surveillance for colorectal cancer with colonoscopy, chemoprevention might be an acceptable alternative. Statins are potent inhibitors of cholesterol biosynthesis. In clinical trials, statins have been found to be beneficial in the primary and secondary prevention of coronary heart disease. However, the overall benefits observed with statins appear to be greater than what might be expected from changes in lipid levels alone, suggesting effects beyond cholesterol lowering. This systematic review aimed to gather information on the possible chemopreventive role of statins in preventing carcinogenesis and tumor promotion by a diverse array of mechanisms in both sporadic and colitis-associated cancer in animal models. The MEDLINE database was thoroughly searched using the following keywords: 'statin, HMG-CoA reductase inhibitor, colon cancer, mice, rats, chemoprevention, colitis-associated cancer'. Additional articles were gathered and evaluated. There are a lot of clinical studies and meta-analyses, as well as a plethora of basic research studies implementing cancer cell lines and animal models, on the chemopreventive role of statins in colorectal cancer (CRC). However, data derived from clinical studies are inconclusive, yet they show a tendency toward a beneficial role of statins against CRC pathogenesis. Thus, more research on the molecular pathways of CRC tumorigenesis as related to statins is warranted to uncover new mechanisms and compare the effect of statins on both sporadic and colitis-associated cancer in animal models. Basic science results could fuel exclusive colitis-associated cancer clinical trials to study the chemopreventive effects of statins and to differentiate between their effects on the two types of CRCs in humans.

Colonic Saturated Fatty Acid Concentrations and Expression of COX-1, but not Diet, Predict Prostaglandin E2in Normal Human Colon Tissue

“…Cholesterol medication use was significantly associated with reduced mRNA expression of PTGES1, and PTGES1 is the synthase that associates with PTGS2 (Table 1). This significant reduction in PTGES1 is consistent with data suggesting use of statins as a potential pharmacological approach for colon cancer prevention (30). Previous research also has indicated that combining NSAID use with cholesterol medications may be useful for CRC prevention and treatment (31).…”

Statin Use Is Associated With Reduced Risk of Colorectal Cancer in Patients With Inflammatory Bowel Diseases

“…In rat intestinal epithelium, this inhibition of isoprenylation by lovastatin was associated with induction of apoptosis which could be reversed by administration of GGPP. Induction of apoptosis has been described in several different mice models with various statins, suggesting a class effect 24 . In addition, statins may reduce formation of aberrant crypt foci and polyps, and reduce tumor metastasis 22 .…”

The dichotomous role of H2S in cancer cell biology? Déjà vu all over again

“…Emerging research suggests that statins may prevent various types of cancers, including colon [182–184] and breast [185–187] as well as ovarian, pancreatic, lung, and lymphomas, reviewed in [188]. Statins inhibit cancer cell proliferation by arresting the cell cycle at the G 1 -S phase and inducing apoptosis [189, 190].…”